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. 2015 Jul 6;2015(7):CD011789.
doi: 10.1002/14651858.CD011789.

Milnacipran for neuropathic pain in adults

Sheena Derry  1 , Tudor Phillips, R Andrew Moore, Philip J Wiffen
Affiliations

Milnacipran for neuropathic pain in adults

Sheena Derry et al. Cochrane Database Syst Rev. .

Abstract

Background: Milnacipran is a serotonin-norepinephrine reuptake inhibitor (SNRI) that is sometimes used to treat chronic neuropathic pain and fibromyalgia. This is an update of an earlier review of milnacipran for neuropathic pain and fibromyalgia in adults originally published in The Cochrane Library Issue 3, 2012. We split that review so that this one looked only at neuropathic pain, and a separate review looks at fibromyalgia.

Objectives: To assess the analgesic efficacy and associated adverse events of milnacipran for chronic neuropathic pain in adults.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE to 23 February 2015, together with reference lists of retrieved papers and reviews.

Selection criteria: We included randomised, double-blind studies of eight weeks' duration or longer, comparing milnacipran with placebo or another active treatment in chronic neuropathic pain.

Data collection and analysis: Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality. We did not carry out any analysis.

Main results: We included a single study of 40 participants with chronic low back pain with a neuropathic component. It found no difference in pain scores between milnacipran 100 mg to 200 mg daily or placebo after six weeks (very low quality evidence). Adverse event rates were similar between treatments, with too few data to draw conclusions (very low quality evidence).

Authors' conclusions: There was no evidence to support the use of milnacipran to treat neuropathic pain conditions.

PubMed Disclaimer

Conflict of interest statement

SD has no conflicts relating to this review or any similar product.

TP has no conflicts relating to this review or any similar product.

RAM has no conflicts relating to this review or any similar product.

PJW has no conflicts relating to this review or any similar product.

For transparency we have received research support from charities, government, and industry sources at various times, but none relate to this review. We are funded by the NIHR for work on a series of reviews informing the unmet need of chronic pain and providing the evidence for treatments of pain.

Figures

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Study flow diagram.
See this image and copyright information in PMC

References

References to studies included in this review

NCT01225068 {published data only}
    1. An exploratory randomized placebo controlled trial of milnacipran in patients with chronic neuropathic low back pain. clinicaltrials.gov/ct2/show/record/NCT01225068 (accessed 23 February 2015). [CTG: NCT01225068]

References to ongoing studies

NCT01288937 {published data only}
    1. A placebo controlled, randomized, double blind trial of milnacipran for the treatment of idiopathic neuropathy pain. clinicaltrials.gov/ct2/show/NCT01288937 (accessed 23 February 2015). [CTG: NCT01288937]

Additional references

Baron 2010
    1. Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurology 2010;9(8):807‐19. [DOI: 10.1016/S1474-4422(10)70143-5] - DOI - PubMed
Baron 2012
    1. Baron R, Wasner G, Binder A. Chronic pain: genes, plasticity, and phenotypes. Lancet Neurology 2012;11(1):19‐21. [DOI: 10.1016/S1474-4422(11)70281-] - DOI - PubMed
Bouhassira 2008
    1. Bouhassira D, Lantéri‐Minet M, Attal N, Laurent B, Touboul C. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain 2008;136(3):380‐7. [DOI: 10.1016/j.pain.2007.08.013] - DOI - PubMed
Cording 2015
    1. Cording M, Derry S, Phillips T, Moore RA, Wiffen PJ. Milnacipran for pain in fibromyalgia in adults. Cochrane Database of Systematic Reviews 2015, Issue 10. [DOI: 10.1002/14651858.CD008244.pub3] - DOI - PMC - PubMed
Dechartres 2013
    1. Dechartres A, Trinquart L, Boutron I, Ravaud P. Influence of trial sample size on treatment effect estimates: meta‐epidemiological study. BMJ 2013;346:f2304. [DOI: 10.1136/bmj.f2304] - DOI - PMC - PubMed
Derry 2012b
    1. Derry S, Moore RA. Topical capsaicin (low concentration) for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews 2012, Issue 9. [DOI: 10.1002/14651858.CD010111] - DOI - PMC - PubMed
Derry 2013
    1. Derry S, Sven‐Rice A, Cole P, Tan T, Moore RA. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews 2013, Issue 2. [DOI: 10.1002/14651858.CD007393.pub3] - DOI - PubMed
Derry 2014
    1. Derry S, Wiffen PJ, Moore RA, Quinlan J. Topical lidocaine for neuropathic pain in adults. Cochrane Database of Systematic Reviews 2014, Issue 7. [DOI: 10.1002/14651858.CD010958.pub2] - DOI - PMC - PubMed
Di Franco 2010
    1. Franco M, Iannuccelli C, Atzeni F, Cazzola M, Salaffi F, Valesini G, et al. Pharmacological treatment of fibromyalgia. Clinical and Experimental Rheumatology 2010;28(6 Suppl 63):S110‐6. - PubMed
Dworkin 2008
    1. Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. Journal of Pain 2008;9(2):105‐21. [DOI: 10.1016/j.jpain.2007.09.005] - DOI - PubMed
Finnerup 2015
    1. Finnerup NB, Attal, N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta‐analysis. Lancet Neurology 2015;14(2):162‐73. [DOI: 10.1016/S1474-4422(14)70251-0] - DOI - PMC - PubMed
Gustorff 2008
    1. Gustorff B, Dorner T, Likar R, Grisold W, Lawrence K, Schwarz F, et al. Prevalence of self‐reported neuropathic pain and impact on quality of life: a prospective representative survey. Acta Anaesthesiologica Scandinavica 2008;52(1):132‐6. - PubMed
Hall 2008
    1. Hall GC, Carroll D, McQuay HJ. Primary care incidence and treatment of four neuropathic pain conditions: a descriptive study, 2002‐2005. BMC Family Practice 2008;9:26. [DOI: 10.1186/1471-2296-9-26] - DOI - PMC - PubMed
Hall 2013
    1. Hall GC, Morant SV, Carroll D, Gabriel ZL, McQuay HJ. An observational descriptive study of the epidemiology and treatment of neuropathic pain in a UK general population. BMC Family Practice 2013;14:28. [DOI: 10.1186/1471-2296-14-28] - DOI - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Altman DG, Sterne JAC. Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Hoffman 2010
    1. Hoffman DL, Sadosky A, Dukes EM, Alvir J. How do changes in pain severity levels correspond to changes in health status and function in patients with painful diabetic peripheral neuropathy?. Pain 2010;149(2):194‐201. [DOI: 10.1016/j.pain.2009.09.017] - DOI - PubMed
Jadad 1996
    1. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Controlled Clinical Trials 1996;17(1):1‐12. [DOI: ] - PubMed
Jensen 2011
    1. Jensen TS, Baron R, Haanpää M, Kalso E, Loeser JD, Rice AS, et al. A new definition of neuropathic pain. Pain 2011;152(10):2204‐5. [DOI: 10.1016/j.pain.2011.06.017] - DOI - PubMed
Kalso 2013
    1. Kalso E, Aldington DJ, Moore RA. Drugs for neuropathic pain. BMJ 2013;347:f7339. [DOI: 10.1136/bmj.f7339] - DOI - PubMed
Katusic 1991
    1. Katusic S, Williams DB, Beard CM, Bergstralh EJ, Kurland LT. Epidemiology and clinical features of idiopathic trigeminal neuralgia and glossopharyngeal neuralgia: similarities and differences, Rochester, Minnesota, 1945‐1984. Neuroepidemiology 1991;10:276‐81. [DOI: 10.1159/000110284] - DOI - PubMed
Kjaergard 2001
    1. Kjaergard LL, Villumsen J, Gluud C. Reported methodologic quality and discrepancies between large and small randomized trials in meta‐analyses. Annals of Internal Medicine 2001;135(11):982‐9. - PubMed
Koopman 2009
    1. Koopman JS, Dieleman JP, Huygen FJ, Mos M, Martin CG, Sturkenboom MC. Incidence of facial pain in the general population. Pain 2009;147(1‐3):122‐7. [DOI: 10.1016/j.pain.2009.08.023] - DOI - PubMed
L'Abbé 1987
    1. L'Abbé KA, Detsky AS, O'Rourke K. Meta‐analysis in clinical research. Annals of Internal Medicine 1987;107:224‐33. - PubMed
Lunn 2014
    1. Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database of Systematic Reviews 2014, Issue 1. [DOI: 10.1002/14651858.CD007115.pub3] - DOI - PMC - PubMed
McQuay 1998
    1. McQuay H, Moore R. An Evidence‐based Resource for Pain Relief. Oxford: Oxford University Press, 1998. [ISBN: 0‐19‐263048‐2]
McQuay 2007
    1. McQuay HJ, Smith LA, Moore RA. Chronic pain. In: Stevens A, Raferty J, Mant J, Simpson S editor(s). Health Care Needs Assessment. Oxford: Radcliffe Publishing Ltd, 2007:519‐600. [ISBN: 978‐1‐84619‐063‐6]
Moisset 2007
    1. Moisset X, Bouhassira D. Brain imaging of neuropathic pain. Neuroimaging 2007;37(Suppl 1):S80‐8. [DOI: 10.1016/j.neuroimage.2007.03.054] - DOI - PubMed
Moore 1998
    1. Moore RA, Gavaghan D, Tramèr MR, Collins SL, McQuay HJ. Size is everything ‐ large amounts of information are needed to overcome random effects in estimating direction and magnitude of treatment effects. Pain 1998;78(3):209‐16. [DOI: 10.1016/S0304-3959(98)00140-7] - DOI - PubMed
Moore 2008
    1. Moore RA, Barden J, Derry S, McQuay HJ. Managing potential publication bias. In: McQuay HJ, Kalso E, Moore RA editor(s). Systematic Reviews in Pain Research: Methodology Refined. Seattle: IASP Press, 2008:15‐24. [ISBN: 978‐0‐931092‐69‐5]
Moore 2009
    1. Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for acute and chronic pain in adults. Cochrane Database of Systematic Reviews 2009, Issue 3. [DOI: 10.1002/14651858.CD007076] - DOI - PMC - PubMed
Moore 2010a
    1. Moore RA, Eccleston C, Derry S, Wiffen P, Bell RF, Straube S, et al. ACTINPAIN Writing Group of the IASP Special Interest Group on Systematic Reviews in Pain Relief, Cochrane Pain, Palliative and Supportive Care Systematic Review Group Editors. "Evidence" in chronic pain ‐ establishing best practice in the reporting of systematic reviews. Pain 2010;150(3):386‐9. [DOI: 10.1016/j.pain.2010.05.011] - DOI - PubMed
Moore 2010b
    1. Moore RA, Moore OA, Derry S, Peloso PM, Gammaitoni AR, Wang H. Responder analysis for pain relief and numbers needed to treat in a meta‐analysis of etoricoxib osteoarthritis trials: bridging a gap between clinical trials and clinical practice. Annals of the Rheumatic Diseases 2010;69(2):374‐9. [DOI: 10.1136/ard.2009.107805] - DOI - PMC - PubMed
Moore 2010c
    1. Moore RA, Smugar SS, Wang H, Peloso PM, Gammaitoni A. Numbers‐needed‐to‐treat analyses ‐ do timing, dropouts, and outcome matter? Pooled analysis of two randomized, placebo‐controlled chronic low back pain trials. Pain 2010;151(3):592‐7. [DOI: 10.1016/j.pain.2010.07.013] - DOI - PubMed
Moore 2010d
    1. Moore RA, Straube S, Paine J, Phillips CJ, Derry S, McQuay HJ. Fibromyalgia: moderate and substantial pain intensity reduction predicts improvement in other outcomes and substantial quality of life gain. Pain 2010;149(3):260‐4. [DOI: 10.1016/j.pain.2010.02.039] - DOI - PubMed
Moore 2011a
    1. Moore RA, Straube S, Paine J, Derry S, McQuay HJ. Minimum efficacy criteria for comparisons between treatments using individual patient meta‐analysis of acute pain trials: examples of etoricoxib, paracetamol, ibuprofen, and ibuprofen/paracetamol combinations after third molar extraction. Pain 2011;152(5):982‐9. [DOI: ] - PubMed
Moore 2011b
    1. Moore RA, Mhuircheartaigh RJ, Derry S, McQuay HJ. Mean analgesic consumption is inappropriate for testing analgesic efficacy in post‐operative pain: analysis and alternative suggestion. European Journal of Anaesthesiology 2011;28(6):427‐32. [DOI: 10.1097/EJA.0b013e328343c569] - DOI - PubMed
Moore 2012a
    1. Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2012, Issue 12. [DOI: 10.1002/14651858.CD008242.pub2] - DOI - PubMed
Moore 2012b
    1. Moore RA, Straube S, Eccleston C, Derry S, Aldington D, Wiffen P, et al. Estimate at your peril: imputation methods for patient withdrawal can bias efficacy outcomes in chronic pain trials using responder analyses. Pain 2012;153(2):265‐8. [DOI: 10.1016/j.pain.2011.10.004] - DOI - PubMed
Moore 2013a
    1. Moore RA, Straube S, Aldington D. Pain measures and cut‐offs ‐ 'no worse than mild pain' as a simple, universal outcome. Anaesthesia 2013;68(4):400‐12. [DOI: 10.1111/anae.12148] - DOI - PubMed
Moore 2013b
    1. Moore A, Derry S, Eccleston C, Kalso E. Expect analgesic failure; pursue analgesic success. BMJ 2013;346:f2690. [DOI: 10.1136/bmj.f2690] - DOI - PubMed
Moore 2014a
    1. Moore RA, Derry S, Taylor RS, Straube S, Phillips CJ. The costs and consequences of adequately managed chronic non‐cancer pain and chronic neuropathic pain. Pain Practice 2014;14(1):79‐94. [DOI: 10.1111/papr.12050] - DOI - PubMed
Moore 2014b
    1. Moore RA, Wiffen PJ, Derry S, McQuay HJ. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2014, Issue 4. [DOI: 10.1002/14651858.CD007938.pub3] - DOI - PMC - PubMed
Moore 2014c
    1. Moore RA, Cai N, Skljarevski V, Tölle TR. Duloxetine use in chronic painful conditions ‐ individual patient data responder analysis. European Journal of Pain 2014;139(2):477‐9. [DOI: 10.1002/j.1532-2149.2013.00341.x] - DOI - PMC - PubMed
Moulin 2014
    1. Moulin D, Boulanger A, Clark AJ, Clarke H, Dao T, Finley GA, et al. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Research and Management 2014;19(6):328‐35. - PMC - PubMed
NICE 2013
    1. National Institute for Health and Care Excellence (NICE). Neuropathic pain ‐ pharmacological management: the pharmacological management of neuropathic pain in adults in non‐specialist settings, 2013. www.nice.org.uk/guidance/cg173 (accessed 23 February 2015).
Nüesch 2010
    1. Nüesch E, Trelle S, Reichenbach S, Rutjes AW, Tschannen B, Altman DG, et al. Small study effects in meta‐analyses of osteoarthritis trials: meta‐epidemiological study. BMJ 2010;341:c3515. [DOI: 10.1136/bmj.c3515] - DOI - PMC - PubMed
O'Brien 2010
    1. O'Brien EM, Staud RM, Hassinger AD, McCulloch RC, Craggs JG, Atchison JW, et al. Patient‐centered perspective on treatment outcomes in chronic pain. Pain Medicine 2010;11(1):6‐15. [DOI: 10.1111/j.1526-4637.2009.00685.x] - DOI - PubMed
O'Connor 2009
    1. O'Connor, AB, Dworkin RH. Treatment of neuropathic pain: an overview of recent guidelines. American Journal of Medicine 2009;122(10 Suppl):S22‐32. [DOI: 10.1016/j.amjmed.2009.04.007] - DOI - PubMed
Pae 2009
    1. Pae CU, Marks DM, Shah M, Han C, Ham BJ, Patkar AA, et al. Milnacipran: beyond a role of antidepressant. Clinical Neuropharmacology 2009;32(6):355‐63. [DOI: 10.1097/WNF.0b013e3181ac155b] - DOI - PubMed
PaPaS 2012
    1. PaPaS author and referee guidance. papas.cochrane.org/papas‐documents (accessed 23 February 2015).
Rappaport 1994
    1. Rappaport ZH, Devor M. Trigeminal neuralgia: the role of self‐sustaining discharge in the trigeminal ganglion. Pain 1994;56:127‐38. - PubMed
RevMan 2014 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Saarto 2007
    1. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD005454.pub2] - DOI - PMC - PubMed
Soni 2013
    1. Soni A, Batra R, Gwilym S, Spector T, Hart D, Arden N, et al. Neuropathic features of joint pain: a community‐based study. Arthritis & Rheumatism 2013;65(7):1942‐9. [DOI: 10.1002/art.37962] - DOI - PMC - PubMed
Straube 2008
    1. Straube S, Derry S, McQuay HJ, Moore RA. Enriched enrollment: definition and effects of enrichment and dose in trials of pregabalin and gabapentin in neuropathic pain. A systematic review. British Journal Clinical Pharmacology 2008;66(2):266‐75. [DOI: 10.1111/j.1365-2125.2008.03200.x] - DOI - PMC - PubMed
Straube 2010
    1. Straube S, Derry S, Moore RA, Paine J, McQuay HJ. Pregabalin in fibromyalgia ‐ responder analysis from individual patient data. BMC Musculoskeletal Disorders 2010;11:150. [DOI: 10.1186/1471-2474-11-150] - DOI - PMC - PubMed
Sultan 2008
    1. Sultan A, Gaskell H, Derry S, Moore RA. Duloxetine for painful diabetic neuropathy and fibromyalgia pain: systematic review of randomised trials. BMC Neurology 2008;8:29. [DOI: 10.1186/1471-2377-8-29] - DOI - PMC - PubMed
Suzuki 2004
    1. Suzuki R, Rygh LJ, Dickenson AH. Bad news from the brain: descending 5‐HT pathways that control spinal pain processing. Trends in the Pharmacological Sciences 2004;2512:613‐7. - PubMed
Torrance 2006
    1. Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. Journal of Pain 2006;7(4):281‐9. [DOI: 10.1016/j.jpain.2005.11.008] - DOI - PubMed
Tracey 2011
    1. Tracey I. Can neuroimaging studies identify pain endophenotypes in humans?. Nature Reviews Neurology 2011;7(3):173‐81. [DOI: 10.1038/nrneurol.2011.4] - DOI - PubMed
Treede 2008
    1. Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 2008;70(18):1630‐5. [DOI: 10.1212/01.wnl.0000282763.29778.59] - DOI - PubMed
van Hecke 2014
    1. Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain 2014;155(4):654‐62. [DOI: 10.1016/j.pain.2013.11.013] - DOI - PubMed
Vo 2009
    1. Vo T, Rice AS, Dworkin RH. Non‐steroidal anti‐inflammatory drugs for neuropathic pain: how do we explain continued widespread use?. Pain 2009;143(3):169‐71. [DOI: 10.1016/j.pain.2009.03.013] - DOI - PubMed
von Hehn 2012
    1. Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron 2012;73(4):638‐52. [DOI: 10.1016/j.neuron.2012.02.008] - DOI - PMC - PubMed
Vos 2012
    1. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990‐2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380(9859):2163‐96. [DOI: 10.1016/S0140-6736(12)61729-2] - DOI - PMC - PubMed
Wiffen 2013
    1. Wiffen PJ, Derry S, Moore RA, Aldington D, Cole P, Rice ASC, et al. Antiepileptic drugs for neuropathic pain and fibromyalgia ‐ an overview of Cochrane reviews. Cochrane Database of Systematic Reviews 2013, Issue 11. [DOI: 10.1002/14651858.CD010567.pub2] - DOI - PMC - PubMed

References to other published versions of this review

Derry 2012a
    1. Derry S, Gill D, Phillips T, Moore RA. Milnacipran for neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2012, Issue 3. [DOI: 10.1002/14651858.CD008244.pub2] - DOI - PMC - PubMed

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